Effect of IAPP on the proteome of cultured Rin-5F cells

Background

Islet amyloid polypeptide (IAPP) or amylin deposits can be found in the islets of type 2 diabetes patients. The peptide is suggested to be involved in the etiology of the disease through formation of amyloid deposits and destruction of β islet cells, though the underlying molecular events leading from IAPP deposition to β cell death are still largely unknown.

Results

We used OFFGEL? proteomics to study how IAPP exposure affects the proteome of rat pancreatic insulinoma Rin-5F cells. The OFFGEL? methodology is highly effective at generating quantitative data on hundreds of proteins affected by IAPP, with its accuracy confirmed by In Cell Western and Quantitative Real Time PCR results. Combining data on individual proteins identifies pathways and protein complexes affected by IAPP. IAPP disrupts protein synthesis and degradation, and induces oxidative stress. It causes decreases in protein transport and localization. IAPP disrupts the regulation of ubiquitin-dependent protein degradation and increases catabolic processes. IAPP causes decreases in protein transport and localization, and affects the cytoskeleton, DNA repair and oxidative stress.

Conclusions

Results are consistent with a model where IAPP aggregates overwhelm the ability of a cell to degrade proteins via the ubiquitin system. Ultimately this leads to apoptosis. IAPP aggregates may be also toxic to the cell by causing oxidative stress, leading to DNA damage or by decreasing protein transport. The reversal of any of these effects, perhaps by targeting proteins which alter in response to IAPP, may be beneficial for type II diabetes.

     

A speech-to-noise ratio measurement algorithm

An algorithm to measure speech-to-noise ratios has been implemented on a minicomputer. The algorithm attributes the energy within each consecutive 20-ms frame of a speech-plus-noise waveform to either a speech or noise source. This discrimination process is based upon the known characteristics of frame energy histograms of such waveforms. In response to observed inaccuracies of this discrimination process in cases of low speech versus noise separation, a method of estimating the speech Vrms of the signal is incorporated which attempts to recover speech energy, "masked" by noise. The algorithm's ability to track known speech-to-noise ratios on a decibel-for-decibel basis down to a ratio of approximately 5 dB has been demonstrated by experimentation.     

Application of liquid chromatography-tandem mass spectrometry to the analysis of benzodiazepines in blood

A sensitive and selective high-performance liquid chromatography/atmospheric pressure chemical ionisation tandem mass spectrometry (HPLC/APCI-MS/MS) method for the simultaneous detection of 18 benzodiazepines and metabolites in human blood is described. The procedure utilises butyl chloride extraction at alkaline pH followed by reversed-phase liquid chromatography. The technique is suitable for screening analyses and confirmation of identity of the benzodiazepines at their lowest reported therapeutic concentrations using 500 microL of blood. The method has been successfully applied in forensic cases involving low concentrations of benzodiazepines.     

Nanostructures of gold coated iron core-shell nanoparticles and the nanobands assembled under magnetic field

Pure metal iron nanoparticles are unstable in the air. By a coating iron on nanoparticle surface with a stable noble metal, these air-stable nanoparticles are protected from the oxidation and retain most of the favorable magnetic properties, which possess the potential application in high density memory device by forming self-assembling nanoarrays. Gold-coated iron core-shell structure nanoparticles (Fe/Au) synthesized using reverse micelles were characterized by transmission electron microscopy (TEM). The average nanoparticle size of the core-shell structure is about 8 nm, with about 6 nm diameter core and 1∼2 nm shell. Since the gold shell is not epitaxial growth related to the iron core, the morié pattern can be seen from the overlapping of iron core and gold shell. However, the gold shell lattice can be seen by changing the defocus of TEM. An energy dispersive X-ray spectrum (EDS) also shows the nanoparticles are air-stable. The magnetic measurement of the nanoparticles also proved successful synthesis of gold coated iron core-shell structure. The nanoparticles were then assembled under 0.5 T magnetic field and formed parallel nanobands with about 10 μm long. Assembling two dimensional ordered nanoarrays are still under going. Received 29 November 2000     

An Algebraic Analogue of Exel–Pardo C∗-Algebras

Algebras and Representation Theory - We introduce an algebraic version of the Katsura C?-algebra of a pair A,B of integer matrices and an algebraic version of the Exel–Pardo...     

Chatter, process damping, and chip segmentation in turning: A signal processing approach

An increasing number of aerospace components are manufactured from titanium and nickel alloys that are difficult to machine due to their thermal and mechanical properties. This limits the metal removal rates that can be achieved from the production process. However, under these machining conditions the phenomenon of process damping can be exploited to help avoid self-excited vibrations known as regenerative chatter. This means that greater widths of cut can be taken so as to increase the metal removal rate, and hence offset the cutting speed restrictions that are imposed by the thermo-mechanical properties of the material. However, there is little or no consensus as to the underlying mechanisms that cause process damping.The present study investigates two process damping mechanisms that have previously been proposed in the machining literature: the tool flank/workpiece interference effect, and the short regenerative effect. A signal processing procedure is employed to identify flank/workpiece interference from experimental data. Meanwhile, the short regenerative model is solved using a new frequency domain approach that yields additional insight into its stabilising effect. However, analysis and signal processing of the experimentally obtained data reveals that neither of these models can fully explain the increases in stability that are observed in practice. Meanwhile, chip segmentation effects were observed in a number of measurements, and it is suggested that segmentation could play an important role in the process-damped chatter stability of these materials.     

Single-molecule dynamics of lysozyme processing distinguishes linear and cross-linked peptidoglycan substrates

The dynamic processivity of individual T4 lysozyme molecules was monitored in the presence of either linear or cross-linked peptidoglycan substrates. Single-molecule monitoring was accomplished using a novel electronic technique in which lysozyme molecules were tethered to single-walled carbon nanotube field-effect transistors through pyrene linker molecules. The substrate-driven hinge-bending motions of lysozyme induced dynamic electronic signals in the underlying transistor, allowing long-term monitoring of the same molecule without the limitations of optical quenching or bleaching. For both substrates, lysozyme exhibited processive low turnover rates of 20-50 s(-1) and rapid (200-400 s(-1)) nonproductive motions. The latter nonproductive binding events occupied 43% of the enzyme's time in the presence of the cross-linked peptidoglycan but only 7% with the linear substrate. Furthermore, lysozyme catalyzed the hydrolysis of glycosidic bonds to the end of the linear substrate but appeared to sidestep the peptide cross-links to zigzag through the wild-type substrate.